In order to inhibit mature hepatocytes regeneration and increase check details hepatic progenitor cell expansion and differentiation, the treated rats were fed with 2-AAF during the period of cirrhosis progression. The results showed that the expressions of hepatic oval cell markers (OV6 and CK19) were increased significantly during fibrosis progression. In the CCl4/ 2-AAF treated rats, OV6 positive cells

and CK19 positive cells extended across the liver lobule, formed bridges between portal tracts and divided the parenchyma into smaller pseudolobules, as determined by immunohistochemitry. Double staining showed that OV6 was largely colocated with α-SMA positive cells, and the number of cells positive for both OV6 and α-SMA was obviously increased after administration of 2-AAF. The expressions of Wnt4, Wnt5b, frizzled2, frizzled3 and frizzled6 were markedly increased after administration of 2-AAF (p<0.01). Immunohistochemistry showed that p-catenin protein was

mostly localized to the nucleus of cells before administration of 2-AAF; however, p-catenin was found predominantly within the cytoplasm after administration of 2-AAF. In addition, the expression level of p catenin was not changed by the administration of 2-AAF, suggesting that the activation of Wnt pathways was not mediated through the classical p-catenin pathway. Moreover, after administration of 2-AAF, gene expression of frizzled1 and frizzled4 was markedly decreased (p<0.01); however frizzled5 expression was not significantly changed, indicating that non-canonical Wnt signaling rather Lenvatinib mw than Wnt/p-catenin signaling was primarily activated. We also determined that the expression of TGF-β1 was markedly increased in vivo after administration of 2-AAF. Expression of α-SMAand F-actin, as well as collagen types 上海皓元医药股份有限公司 I and IV were significantly increased after the WB-F344 cell line, was treated with TGB-p1 for 24 hours. Additional investigation revealed that both Wnt5b and frizzled2 expression were significantly

increased in WB-F344 cells after treatment with TGF-β1 (p < 0.01), and p-catenin expression was not up-regulated during the treatment. Thus, these in vitro results confirmed our finding in vivo. In conclusion, our results indicate that hepatic progenitor cells appear to transdifferentiate into myofibroblasts and exhibit a profibrotic effect in the fibrogenic process through activating the non-canonical Wnt signaling pathway. Disclosures: The following people have nothing to disclose: Jiamei Chen, Yongping Mu, Yuyou Duan, Ping Liu Background: Activation of the FXR and TGR5 bile acid receptor pathways with the dual agonist INT-767 has been shown to improve non-alcoholic fatty liver disease (NAFLD) in a murine diet-induced obesity model. While the mechanisms of the liver improvement remain to be fully elucidated direct effects of these pathways on hepatocyte and macrophage function have been demonstrated.